Phenylsilane:An Efficient Coupling Reagent For Amide And Peptide Synthesis

As is well known as important class of compounds,amide is not only as the important part to constitute in the basic structure of protein elements,but also consist in many natural products,pharmaceuticals,pesticides and materials.Therefore,the development of efficient and green amide synthesis method is not only in the field of synthetic chemistry,but also has a very important significance in chemical biology.The condensation reaction of a carboxylic acid with an amine acylation is currently the most widely used method of amide synthesis.However,many current condensing employed agent caused the by-product in the reaction,which is difficult to remove.In addition,because of its strong Lewis alkaline used,the amino acid in the reaction process occurs racemization.In view of the neutral characteristics of organosilicon compounds and the possibility that they can be easily hydrolyzed and removed as the condensation reagents in the reaction of siloxanes.In this paper,the commercially available silicon hydrogens are used as coupling reagents,amine and amino acid condensation acylation reaction carried out a series of research work:1.Reaction of carboxylic acid and amide to form amide directlyIn this paper,we first investigated a condensation acylation reaction by using carboxylic acid and primary amine as a simple template.Then,hydrosilylation agent and its amount,the reaction solvent,the ratio of carboxylic acids and amines conditions were studied to establish the optimal conditions:It is found that phenyl silane can efficiently promote the reaction at room temperature.In addition,further purification of the product is very simple-just to generate silicon oxide by-product by hydrolyzed,then extraction without tedious chromatographic purification can be separated chromatographically to get pure amide product.On this basis,we further investigated the substrate scope of the reaction and found that both either aliphatic or aromatic carboxylic acid and primary or secondary amine can be successfully applied to the reaction and to obtain an excellent yield.2.Synthesis of Dipeptides by Coupling Amino Acids with Amino AcidsAfter successfully realizing the amidation of carboxylic acids with amines,we also studied the condensation reaction of amino acids with low reactivity.It was found that using phenyl silane as a coupling reagent,the amino acid derivative can get corresponding dipeptide with moderate to excellent yields at fifty degree.In addition,we have also studied the coupling reaction of amino acid substrates such as amino acid H-L-Phe-OMe with the phenylglycine derivative Boc-D-Phg-OH,which can easily be racemized.It is pleased that we can get the corresponding dipeptide Boc-D-Phg-L-Phe-OMe at 90%ee value.Finally,the mechanism of this reaction was investigated by in situ NMR,including 1H NMR,13C NMR and 29Si {H} NMR.It was found that the dehydrogenation reaction of phenyl silane and carboxylic acid by was able to proceed smoothly key.It is found that the dehydrogenation of phenyl silane with carboxylic acid catalyzed by the substrate amine is the key to the smooth progress of the reaction.